In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Ischemic stroke (IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its potent neuroprotective properties. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mitophagy/drug effects* ; Resveratrol/analogs & derivatives* ; Neuroprotective Agents/pharmacology* ; Humans ; Neurons/metabolism* ; Reactive Oxygen Species/metabolism* ; Ischemic Stroke/genetics* ; Male ; Quinolines/pharmacology* ; Mice ; Fallopia japonica/chemistry* ; Mitochondria/metabolism* ; Reperfusion Injury/metabolism* ; Rats ; Mice, Inbred C57BL ; Disease Models, Animal

Objective:To assess the usage of the robot-assisted core-needle biopsy for the bone tumors, moreover to compare its outcomes with the manual technique.Methods:A retrospective study was conducted from February 2019 to February 2021, the medical records of the patients with bone lesions that had received core-needle biopsy were collected. There were 57 males and 45 females, the age was 45.9 (10~79) years. Eight patients received robot-assisted biopsy, whereas 94 patients underwent C-arm/ CT guided biopsy, the recorded data included operational duration, aspirational direction adjustment, etc. The pathological diagnosis reports of the biopsy specimens and the operational specimens were compared.Results:The diagnosis outcomes included metastases (33 cases), osteosarcoma (12 cases), chondrosarcoma (12 cases), giant cell tumor of bone (12 cases), fibrous dysplasia (7 cases), chronic osteomyelitis (7 cases), lymphoma (4 cases), multiple myeloma (4 cases), chronic fracture (3 cases), chondroblastoma (2 cases), pleomorphic undifferentiated sarcoma (2 cases), leiomyosarcoma (1 case), and Langerhans cell histiocytosis (1 case). Eighty-seven cases (85.29 %) lesions were found in the limbs, whereas 15 cases (14.71%) were in the axial locations. Compared with the manual group, the robot-assisted group had more axial locations: 7/8 vs. 11.70%(11/94), P<0.01; fewer aspirational direction adjustment: (0.4 ± 0.1) times vs. (3.1 ± 1.5) times, P<0.01 ; longer operational duration: (48.8 ± 8.8) min vs. (29.6 ± 6.0) min, P<0.01. There were no statistical differences between the two groups regarding the sex, age, pathological fracture, diagnostic accuracy, open biopsy rate and complications ( P>0.05). Conclusions:The robot-assisted core-needle biopsy is a reliable technique, it helps decrease the operational difficulty. The usage of this technique is recommendable for the bone lesions with great difficulty for biopsy, such as the minimal bone tumors and the lesions in the spine and the pelvis.

Objective:To explore the application value of histogram and texture feature analysis based on CT images in distinguishing long bone osteosarcoma (OS) from Ewing sarcoma (ES).Methods:A retrospective collection of 25 patients with long bone osteosarcoma and 25 patients with Ewing sarcoma confirmed by surgery and pathology in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Qilu Hospital of Shandong University and Nanjing Drum Tower Hospital, Nanjing University Medical School, from March 2018 to May 2023 was conducted. All patients were randomly divided into a training set (21 cases of OS and 19 cases of ES) and a validation set (4 cases of OS and 6 cases of ES) in an 8∶2 ratio. The region of interest (ROI) on CT images to extract texture feature parameters was manually sketched. Random forest and least absolute shrinkage and selection operator (LASSO) algorithm were used for feature screening. Logistic regression (LR), random forest (RF), support vector machine (SVM) and K-nearest neighbor (KNN) classifiers were used to establish models respectively. Receiver operating characteristic (ROC)curve was drawn and area under the curve (AUC) was calculated to evaluate the diagnostic efficiency of the four models.Results:A total of 100 texture parameters were extracted from CT images, and 8 feature parameters (maximum 3D diameter, 10th percentile, kurtosis, maximum pixel intensity value, inverse normalization, grayscale level variance, long range high grayscale emphasis, and low grayscale area emphasis) were obtained through screening. Four classifiers were used to establish models, and the AUC values of the four models (LR, RF, SVM, KNN) in the validation group were 0.92, 0.79, 0.83, and 0.73, respectively. LR and SVM classifier algorithm trains models had high diagnostic efficiency, with an accuracy of 90%, sensitivity of 83%, specificity of 100%, and AUC of 92% for the LR classifier validation set; the accuracy of SVM classifier validation set was 80%, sensitivity was 67%, specificity was 100%, and AUC was 83%.Conclusions:LR and SVM models have high value in distinguishing OS and ES.

Objective:To explore the diagnostic value of magnetic resonance imaging (MRI) Q-Dixon fat quantification technique in differentiating vertebral metastases from hemangiomas in cancer patients.Methods:A retrospective analysis was conducted on 20 patients with vertebral metastases and 8 with vertebral hemangiomas who underwent vertebral MRI scans at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from December 2021 to December 2023. Two radiologists independently measured the fat fractions (FF) in three areas (the lesion area, the normal area of the same vertebra, and the normal area of an adjacent vertebra) and evaluated the consistency of measurements. Group differences were tested using independent sample t-tests or Mann-Whitney U tests, and diagnostic performance was assessed by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results:There was very high inter-observer consistency in the FF measurements across the three regions. The FF in the lesion areas of vertebral metastases group was significantly lower than that in the vertebral hemangioma group (13.8 ± 11.5 vs. 56.5 ± 22.1), there was statistical difference ( P<0.01). There were no significant differences in the FF of normal vertebral areas between the two groups ( P>0.05). ROC curve analysis showed that FF could differentiate vertebral metastases from hemangiomas with an AUC of 0.931, a specificity of 90%, and a sensitivity of 87.5%. Conclusions:The FF measured by the Q-Dixon quantitative fat technique can accurately differentiate between vertebral hemangiomas and vertebral metastases, providing more precise guidance for the diagnosis of vertebral lesions.

Objective:To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL).Methods:This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors.Results:Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×10 9/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively ( χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant ( χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively ( χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%, χ2=4.13, P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%, χ2=4.06, P=0.044;(58.3±18.6)% vs. (85.7±3.2)%, χ2=9.44, P=0.002). Multivariate analysis showed that age ( OR=0.58, 95% CI 0.35-0.97) and white blood cell count at first diagnosis ( OR=0.43, 95% CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 ( OR=0.55,95% CI 0.31-0.97), ETV6-RUNX1 fusion gene ( OR=0.13,95% CI 0.03-0.54), MLL gene rearrangement ( OR=2.55,95% CI 1.18-5.53) and white blood cell count at initial diagnosis ( OR=0.52,95% CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions:The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

As essential part of teachers' teaching practice, the design and arrangement of assignments is the main carrier of interaction between teachers and students, and is also an important learning way for students. According to the discipline characteristics and teaching modes of histology and embryology courses, we have developed a systematic assignment design model that covers theory, practice, and application with four types of assignments—pre-class assignments, exploratory assignments, practical assignments, and innovative assignments distributed before class, in class, after class, and throughout the teaching process. Behind this assignment design strategy is the concept of learner-centered teaching, which aims to help students learn professional knowledge and develop comprehensive literacy.

Objective:To explore the association between environment exposure and hormone-sensitive cough in patients with chronic cough.Methods:Clinical data of 197 patients with chronic cough visited outpatient clinic of the Second Affiliated Hospital of Guangzhou Medical University from June 2016 to June 2021 were retrospectively analyzed, including 130 cases of corticosteroid responsive cough (CRC, 66.0%) and 67 cases of non-corticosteroid responsive cough (NCRC, 34.0%). The association between living environment exposure and hormone sensitivity was examined with a binary logistic regression analysis.Results:Among 197 patients with chronic cough, there were 82 males (41.6%) and 115 females (58.4%). 75.1% (148/197) had a history of smoking, and 16.8% (33/197) had a history of allergies. 66.0% (130/197) lived in the city center, 18.3% (36/197) had a chemical factory around their place of residence, 11.2% (22/197) renovated their homes within the first six months of the disease, 15.7% (31/197) purchase new furniture, 54.3% (107/197) plant flowers and plants in their houses, 21.3% (42/197) keep pets in their houses, 79.2% (156/197) had lived in their houses for more than 2 years, 71.1% (140/197) had cockroaches in their houses, 16.2% (32/197) had mold in their houses, 83.3% (164/197) had a frequency of air conditioning cleaning exceeds 2 months per time.There were 130 patients (66.0%) with CRC and 67 patients (34.0%) with NCRC.Binary logistic regression analysis showed that living close to the main road ( OR=2.296, 95% CI: 1.350-3.904, P=0.002), living near chemical factories ( OR=3.322, 95% CI: 2.158-5.573, P<0.001), history of allergy ( OR=2.175, 95% CI: 1.165-4.058, P=0.015), purchasing new furniture within 6 months ( OR=2.828, 95% CI: 1.402-5.706, P=0.004), cotton and linen curtains ( OR=1.875, 95% CI: 1.038-3.388, P=0.037) were positively correlated with CRC; while down and wool pillowcases and quilts ( OR=0.142, 95% CI: 0.033-0.602, P=0.008; OR=0.207, 95% CI: 0.067-0.640, P=0.006) and low ventilation frequency ( OR=0.281, 95% CI: 0.131-0.603, P=0.001) were negatively correlated with CRC. Conclusion:Hormone-sensitive cough patients account the most of chronic cough cases, and there are differences in the living environment exposure between CRC and NCRC patients, which provides information for corresponding interventions to prevent and manage CRC.

Objective:To investigate the long-term prognosis of liver transplantation (LT) recipients who received grafts from donors aged ≥80 years and the associated risk factors.Methods:Clinical and follow-up data of LT recipients from January 2002 to June 2023 were retrospectively analyzed using the United Network for Organ Sharing (UNOS) database. Donors were categorized into three groups : non-elderly donors (NED, age < 60 years), elderly donors (ED, age 60-79 years), and very elderly donors (VED, age ≥80 years). Propensity score matching (PSM) was used to reduce baseline selection bias among the groups. Survival rates were calculated using the Kaplan-Meier method, and differences among the groups were compared using the Log-Rank test. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent risk factors for overall survival (OS) in the VED group. Recipients were further subdivided into three age groups (<50 years, 50-69 years, and ≥70 years) to compare survival outcomes among NED, ED, and VED groups.Results:A total of 115, 089 LT recipients were included, comprising 95, 973 (83.4%) in the NED group, 18, 520 (16.1 %) in the ED group, and 596 (0.5 %) in the VED group. After 3∶3∶1 PSM, each group included 1, 623 recipients for NED and ED, and 541 for VED, with no significant differences in baseline data. The 10-year OS rates for NED, ED, and VED groups were 61.8%, 55.9%, and 47.8%, respectively, and the 10-year graft survival (GS) rates were 61.3 %, 53.8%, and 45.9 %, respectively, with all comparisons showing statistical significance ( P< 0.001). In recipients aged <70 years, the VED group had significantly lower OS and GS rates (49.0% and 47.1 %, respectively ) compared to the NED (63.7 % and 61.8%) and ED (57.7% and 55.2 %) groups ( P< 0.001 ). For recipients aged ≥70 years, there were no significant differences in 10-year OS and GS among the NED (47.2% and 48.7 %), ED (47.0 % and 48.7 %), and VED (40.0 % and 39.2 %) groups ( P= 0.992 and P= 0.996, respectively). Cox regression analysis identified cold ischemia time ≥8 hours ( HR=1.447, 95% CI: 1.088-1.923, P=0.011), pre-transplant ICU dependence ( HR=1.803, 95% CI: 1.176–2.765, P=0.007), and hepatitis B/C virus infection ( HR =1.432, 95% CI: 1.057-1.941, P=0.020) as independent risk factors for OS in the VED group. Conclusions:Liver grafts from VED grafts significantly reduce long-term OS and GS in recipients, except in those aged ≥70 years where prognosis is comparable to recipients of NED and ED grafts.. For the VED group, factors such as cold ischemia time ≥8 hours, pre-transplant ICU dependence, and hepatitis B/C virus infection markedly influence the prognosis.

Objective:To explore the role of ductular reaction in assessing the efficacy of liver transplantation.Method:From January 2015 to December 2020, he relevant clinical data were retrospectively reviewed for 100 recipients and their corresponding donors at Shulan (Hangzhou) Hospital. They were assigned into two groups of hepatic steatosis (HS group, 65 cases) and non-hepatic steatosis (non-HS group, 35 cases) according to whether or not receiving steatosis donated liver. Furthermore, based upon the occurrence of early allograft dysfunction (EAD), the participants were categorized into two groups of EAD (33 cases) and non-EAD (67 cases). The degree of bile duct reaction ductular reaction was defined by the percentage of staining area occupied by cytokeratin 19 (CK19) -positive bile duct cells in immunohistochemical-stained specimens. Donor of ductular reaction were compared between HS/non-HS and EAD/non-EAD groups. The risk factors for EAD were identified by univariate and multivariate Logistic regression analysis. Subgroup analysis was conducted based upon the level of ductular reaction (DR number) in donors (DR=0.4 as a threshold) and whether or not donors exhibited steatosis. The impact of DR was examined on the incidence of EAD and survival post-liver transplantation in steatosis donors.Result:The level of DR was higher in steatosis donor than that in non-steatosis donor [ (0.59%±0.385%) vs. (0.32%±0.194%), P<0.01]. And it was higher in EAD group than that in non-EAD group [ (0.72%±0.449%) vs. (0.38%±0.226%), P<0.01]. Multivariate logistic regression analysis showed that a high level of ductular reaction was an independent risk factor for EAD post-liver transplantation in donor. Subgroup analysis revealed that receiving a steatosis donor with low ductular reaction (DR<0.4%) had comparable levels of EAD occurrence and overall survival rate to receiving a non-steatosis donor. Conclusion:Steatosis with low ductular reaction donor may be safely applied for liver transplantation. And assessing donor injury based upon ductular reaction can effectively expand the clinical application of steatosis donors.